Mesenchymal stem cell‐based therapy: a new paradigm in regenerative medicine

Abstract

Mesenchymal stem cells (MSCs), adherent fibroblastoid cells, present in bone marrow and many other tissues can be easily isolated and expanded in vitro. They are capable of differentiating into different cell types such as osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial cells and neuronal cells. Such immense plasticity coupled with their ability to modulate the activity of immune cells makes them attractive for stem cell-based therapy aimed at treating previously incurable disorders. Preclinical studies have reported successful use of MSCs for delivering therapeutic proteins and repairing defects in a variety of disease models. These studies highlighted the in vivo potential of MSCs and their ability to home to injury sites and modify the microenvironment by secreting paracrine factors to augment tissue repair. Their therapeutic applicability has been widened by genetic modification to enhance differentiation and tissue targeting, and use in tissue engineering. Clinical trials for diseases such as osteogenesis imperfecta, graft-versus-host disease and myocardial infarction have shown some promise, demonstrating the safe use of both allogeneic and autologous cells. However, lack of knowledge of MSC behaviour and responses in vitro and in vivo force the need for basic and animal studies before heading to the clinic. Contrasting reports on immunomodulatory functions and tumorigenicity along with issues such as mode of cell delivery, lack of specific marker, low survival and engraftment require urgent attention to harness the potential of MSC-based therapy in the near future.

Mesenchymal Stem Cells in Chronic Wounds: The Spectrum from Basic to Advanced Therapy

“…Thus, a small amount of bone marrow aspirate is adequate for the expansion into large number of MSCs for transplantation. 96 MSCs are relatively simple to isolate, but extended expansion has been shown to adversely alter their properties. 97 Human MSCs undergo senescence and exhibit decreased differentiation capacity.…”

Angiogenic properties of adipose tissue-derived multipotent mesenchymal stromal cells in patients with coronary heart disease

“…В последнее время прогресс в области лечения этих заболеваний связывают с методами клеточной терапии. Перспективным источником для клеточной терапии сердечно-сосудистых забо-леваний ишемического генеза признаны мультипо-тентные мезенхимальные стромальные клетки (ММСК) благодаря их способности стимулировать васкуляризацию ишемизированных тканей in vivo [2]. Считается, что их влияние на рост кровеносных сосудов в основном обусловлено паракринными эффектами -способностью секретировать широ-кий спектр факторов роста, цитокинов и хемоки-нов, протеаз, белков внеклеточного матрикса [3].…”

“…Жировая ткань как источник ММСК ЖТ для кле-точной терапии считается наиболее перспективной, так как может быть получена в большом количестве в ходе малоинвазивных хирургических процедур. Терапевтическая эффективность этих клеток изучена во многих экспериментах на клинически релевант-ных моделях патологий у животных [2]. Сегодня известны результаты нескольких клинических испы-таний (APOLLO, PRECISE, MyStromalCell Trial), где была показана возможность лечения острой и хро-нической ИБС с помощью внутрикоронарного вве-дения ММСК ЖТ [4][5][6].…”

Tissue Engineering of Skeletal Muscle

“…Low incorporation rates are the main obstacle for cytotherapie in clinical settings. Though, Satija and co-workers proposed paracrine effects of transplanted MSCs in vivo as an important therapeutic effect (Satija et al 2009). Therefore, transplanted MSCs secrete different cytokines resulting in anti-inflammatory, angiogenic and anti-apoptotic effects (Meirelles Lda & Nardi 2009, Sze et al 2007) and thus facilitate local endogenous tissue repair (Nesselmann et al 2008).…”